title: MicroRNA-323-3p regulates the activity of polycomb repressive complex 2 (PRC2) via targeting the mRNA of embryonic ectoderm development (Eed) gene in mouse embryonic stem cells.
abstract: PRC2 (Polycomb repressive complex 2) mediates epigenetic gene silencing by catalyzing the triple methylation of histone H3 Lys-27 (H3K27me3) to establish a repressive epigenetic state. PRC2 is involved in the regulation of many fundamental biological processes and is especially essential for embryonic stem cells. However, how the formation and function of PRC2 are regulated is largely unknown. Here, we show that a microRNA encoded by the imprinted Dlk1-Dio3 region of mouse chromosome 12, miR-323-3p, targets Eed (embryonic ectoderm development) mRNA, which encodes one of the core components of PRC2, the EED protein. Binding of miR-323-3p to Eed mRNA resulted in reduced EED protein abundance and cellular H3K27me3 levels, indicating decreased PRC2 activity. Such regulation seems to be conserved among mammals, at least between mice and humans. We demonstrate that induced pluripotent stem cells with varied developmental abilities had different miR-323-3p as well as EED and H3K27me3 levels, indicating that miR-323-3p may be involved in the regulation of stem cell pluripotency through affecting PRC2 activity. Mouse embryonic fibroblast cells had much higher miR-323-3p expression and nearly undetectable H3K27me3 levels. These findings identify miR-323-3p as a new regulator for PRC2 and provide a new approach for regulating PRC2 activity via microRNAs.
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Fei
authors.initials: F
authors.lastname: Teng
authors.forename: Guan-Zheng
authors.initials: GZ
authors.lastname: Luo
authors.forename: Meng
authors.initials: M
authors.lastname: Wang
authors.forename: Man
authors.initials: M
authors.lastname: Tong
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Zhao
authors.forename: Liu
authors.initials: L
authors.lastname: Wang
authors.forename: Xiu-Jie
authors.initials: XJ
authors.lastname: Wang
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhou
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D004622:Embryo, Mammalian / Q000166:cytology; D053595:Embryonic Stem Cells / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter / Q000235:genetics; D056945:Hep G2 Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D063151:Polycomb Repressive Complex 2 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C107275:Eed protein, mouse; D006657:Histones; C584442:MIRN323 microRNA, mouse; D035683:MicroRNAs; D012333:RNA, Messenger; D008156:Luciferases; D063151:Polycomb Repressive Complex 2; D008239:Lysine
keywords: Embryonic Stem Cell; Histone Methylation; Induced Pluripotent Stem (iPS) Cell; MicroRNA; Polycomb